AB1460 ACCUMULATED ADVANCED GLYCATION ENDPRODUCTS ARE SIGNIFICANTLY HIGHER IN PATIENTS WITH IMMUNE-MEDIATED INFLAMMATORY DISEASES THAN IN HEALTHY POPULATION.
Authors: L. Triginer, I. Carrión Barberà, L. Tío, T. C. Salman Monte, C. Pérez, L. Polino, A. Ribes, J. Llorente Onaindia, J. Monfort
Journal: Annals of the Rheumatic Diseases (2022)

Background Advanced glycation endproducts (AGEs) are the result of non-enzymatic glycation of proteins, lipids or nucleic acids. In circumstances characterized by increased oxidative and carbonyl stress, such as chronic inflammation, AGEs can be formed more rapidly1, generating reactive oxygen species and activating inflammatory signaling cascades through their chief signaling receptor (commonly abbreviated as RAGE) 2 . This positive feedback of inflammation can play a role in the etiology of immune-mediated inflammatory diseases, more specifically in rheumatoid arthritis (RA), ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE). Objectives To investigate whether the accumulated concentrations of AGEs in patients with SLE, RA or AS are significantly higher than in healthy patients. Methods One hundred thirteen consecutive patients fulfilling ACR/EULAR criteria for RA, 60 patients fulfilling ASAS/OMERACT MRI criteria for AS, 97 patients fulfilling ACR/SLICC criteria for SLE and 527 sex-matched healthy controls were recruited.in cross-sectional study. Exclusion criteria were pregnancy, diabetes mellitus, corticosteroid treatment ≥ 20mg/day and malignant neoplasm. Accumulated AGEs were non-invasively measured by skin autofluorescence (Age Reader Mu Connect, Diagnostics Technologies B.V) and demographic and clinical data were collected. AGEs comparisons between patients and controls were performed by multiple linear regression analysis adjusted by confunders, previously described in literature (age, smoking habit and cardiovascular risk-factors). Age was centered at 55 years. Results Table 1 shows some descriptive characteristics of our cohorts. AGEs adjusted mean was significantly increased in SLE patients compared with matched controls (95% CI [2.27, 2.76] vs [1.66, 1.89], p&lt;0.0001), RA patients and controls (95% CI [2.41, 2.61] vs [1.68, 1.88], p&lt;0.0001) and AS patients and controls (95% CI [2.03, 2.6] vs [1.66, 1.93], p&lt;0.0001). In all 3 models, AGEs were also significantly positive correlated with smoking habit measured by packs per year (p&lt;0.001) and age (p&lt;0.0001). Table 1. Descriptive characteristics of the cohorts SLE RA AS Patients Controls Patients Controls Patients Controls N=96 N=189 N=113 N=240 N=60 N=99 AGEs 2.57 (0.65) 1.98 (0.45) 2.59 (0.58) 2.00 (0.42) 2.26 (0.46) 1.90 (0.46) Age 51.0 [43.0;61.0] 56.0 [52.0;62.0] 58.0 [54.0;65.0] 61.0 [56.0;66.0] 47.5 [41.0;55.0] 53.0 [49.0;57.0] Smoker No 76 (79.2%) 133 (70.4%) 86 (76.1%) 196 (81.7%) 42 (70.0%) 58 (58.6%) Yes 20 (20.8%) 56 (29.6%) 27 (23.9%) 44 (18.3%) 18 (30.0%) 41 (41.4%) Packs/year 0.00 [0.00;10.8] 2.50 [0.00;18.8] 2.50 [0.00;18.0] 0.00 [0.00;12.6] 0.00 [0.00;7.88] 14.9 [2.00;30.6] Hypertension No 74 (77.1%) 116 (61.4%) 77 (68.1%) 146 (60.8%) 53 (88.3%) 75 (75.8%) Yes 22 (22.9%) 73 (38.6%) 36 (31.9%) 94 (39.2%) 7 (11.7%) 24 (24.2%) Obesity No 80 (83.3%) 128 (67.7%) 86 (76.1%) 163 (67.9%) 51 (85.0%) 81 (81.8%) Yes 16 (16.7%) 61 (32.3%) 27 (23.9%) 77 (32.1%) 9 (15.0%) 18 (18.2%) Dyslipidemia No 85 (88.5%) 104 (55.0%) 79 (69.9%) 108 (45.0%) 51 (85.0%) 55 (55.6%) Yes 11 (11.5%) 85 (45.0%) 34 (30.1%) 132 (55.0%) 9 (15.0%) 44 (44.4%) Continuous normal: mean (SD); Continuous non-normal: median [IQR]; Categorical: absolute (relative frequency ) Conclusion Accumulated AGEs in all 3 pathologies are significantly higher than in the healthy controls. The different means of AGEs in each of the diseases, being higher in SLE and lower in AS, may suggest a different participation of AGEs in the immune-mediated mechanisms of each pathology. References [1]K. de Leeuw, R. Graaff et al., Accumulation of advanced glycation endproducts in patients with systemic lupus erythematosus, Rheumatology , Volume 46, Issue 10, October 2007, Pg 1551–1556. [2]Yan S., Ramasamy R. &amp; Schmidt A. Mechanisms of Disease: advanced glycation end-products and their receptor in inflammation and diabetes complications. Nat Rev Endocrinol 4, 285–293 (2008). Disclosure of Interests None declared